Re-Appraisal of Microvascular Inflammation and the Role of Biopsy-Based Transcript Diagnostics.

Authors:
Naesens M, Roufosse C, Haas M, Lefaucheur C, Mannon RB, Adam BA, Aubert O, Böhmig GA, Callemeyn J, Groningen MC, Cornell LD, Demetris AJ, Drachenberg CB, Einecke G, Fogo AB, Gibson IW, Halloran P, Hidalgo LG, Horsfield C, Huang E, Kikić Ž, Kozakowski N, Nankivell B, Rabant M, Randhawa P, Riella LV, Sapir-Pichhadze R, Schinstock C, Solez K, Tambur AR, Thaunat O, Wiebe C, Zielinski D, Colvin R, Loupy A, Mengel M.
Abstract:
The XVI-th Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from 19th-23rd September 2022, as a joint meeting with the Canadian Society of Transplantation. To mark the 30th anniversary of the first Banff Classification, pre-meeting discussions were held on the past, present, and future of the Banff Classification. This report is a summary of the meeting highlights that were most important in terms of their effect on the Classification, including discussions around microvascular inflammation and biopsy-based transcript analysis for diagnosis. In a post-meeting survey, agreement was reached on the delineation of the following phenotypes: (1) “Probable antibody-mediated rejection (AMR)”, which represents DSA-positive cases with some histological features of AMR but below current thresholds for a definitive AMR diagnosis; and (2) “Microvascular inflammation (MVI), DSA-negative and C4d-negative”, a phenotype of unclear cause requiring further study, which represents cases with MVI not explained by DSA. Although biopsy-based transcript diagnostics are considered promising and remain an integral part of the Banff Classification (limited to diagnosis of AMR), further work needs to be done to agree on the exact classifiers, thresholds, and clinical context of use.

Figure 1. The Banff Classification in the context of personalized medicine in kidney transplantation. The Banff Classification for Kidney Allograft

Pathology inscribes itself into a broader framework of personalized medicine and clinical decision support strategies, which can be referred to as

“contextualization.” This framework includes the following: (1) risk stratification that indicates the potential of developing a disease; (2) noninvasive

diagnostic biomarkers that indicate the probability of active disease; (3) biopsy-based diagnostics that confirm the diagnosis (where possible, causal)

and specify disease stage/severity (the focus of the Banff Classification); (4) prognostic markers/systems that predict outcome/impact of the disease

such as iBox; and (5) predictive markers of therapeutic response guiding specific treatment choices. These very different types of markers/tests should

be clearly delineated and not confused, with a very specific context of use for each. In clinical decision-making, all these aspects are considered; an

integrated, multidisciplinary approach is essential.

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